Background: Involving chronically ill patients in the management of their health is widely recognized as a vital component of high-quality health care. However, to assume the role of informed participants, patients need both access to their health information and assistance in interpreting such data. Smartphone technology with SMS text messaging functionality offers a convenient and minimally demanding mechanism for providing such dual capabilities to patients. To date, a number of similar digital tools have been developed for use in various chronic and progressive disease conditions, including rheumatoid arthritis. Objective: This paper aims to describe the development of a research protocol that applies a human-centered design (HCD) approach to develop a mobile health (mHealth) intervention to support symptom management and treatment adherence for rheumatoid arthritis. Methods: To guide the development of the mHealth intervention for use within a commercial biotechnology context, we selected and applied an HCD framework consisting of three phases: understanding, ideation, and implementation. Results: Leveraging the framework, we mapped the key objectives and research questions to each phase and identified the HCD techniques and methods most suitable for addressing them. In addition, we identified the need to include a fourth phase, one that referred to postimplementation assessment, which would enable evaluation of patient engagement and intervention impact on symptom self-management. Conclusions: This paper presents a research protocol that applied an HCD framework to guide the development of an mHealth intervention within a commercial biotechnology context. This type of guidance is salient because commercial entities are becoming one of the leading producers of this type of intervention. However, the methodologies used and challenges faced from a research and development perspective are not well-represented in the published research literature to date. Our application of the HCD framework yielded important findings. Each phase of the HCD framework provided important guidance for increasing the likelihood that the final product would be understandable, acceptable, feasible, and engaging to use. Consistent with other researchers in the field of mHealth interventions, we identified the need to add a fourth phase to the HCD framework, one that focused on a postimplementation assessment to guide further improvements to support adoption in real-world settings. [ABSTRACT FROM AUTHOR]